Clinical Projects A. Metformin and longevity In the last decade, research on aging found that metformin use was associated with a reduction in cognitive decline and a longer survival among diabetics compared to those treated with other oral agent. The U.S Food and Drug Administration (FDA) recently approved the first human study to see if an anti-diabetic medication, Metformin, can protect diabetic patients from the multiple diseases from aging. We identified about 300,000 Medicare beneficiaries who were diagnosed with type 2 diabetes post 12/31/2006 and followed them until death, switching to capitated plans, disenrollment from Medicare or 12/31/2016 whichever comes first. During this follow-up, we also collected patients socio-demographic information as well as the use of prescription drugs. Prescription medications include not only 8 commonly prescribed antidiabetics (metformin, insulin, sulfonylureas, thiazolidinedione, GLP-1 analogues, DPP-4 inhibitors, SGLT-2 inhibitors, and other glucose lowering drugs), but also 5 antihypertensive medications (diuretics, beta-blockers, calcium-channel blockers, ACE inhibitors, and ARBs) and 1 lipid-lowering drug (statin). Controlling for other medication use and patients characteristics in time-varying manner, metformin was not strongly associated with the longer survival (HR=0.95) and the association was not statistically significant. Rather, Compare to the no use of each study medication, mortality risk declined with use of 3 diabetes drugs (SGLT-2 inhibitors, GLP-1 analogues and DPP-4 Inhibitors) 3 blood pressure medications (diuretics, ARBs, and ACEI inhibitors) and statins. Statin exhibited most consistent, reduction in all-cause mortality risk but 20% of study patients never took a statin, suggesting missed prevention opportunities. This study was currently under review. B. Proton Pump Inhibitors (PPIs) and mortality Proton pump inhibitors (PPIs) have been associated with increases in the incidence of pneumonia, C Decile infection and osteoporosis/fractures, probable chronic renal failure and cardiac events. Xie et al reported that PPIs could also increase the risk of death using Veterans Affairs (VA) data (HR of 1.15 1.25). From 2007-2016 Medicare Parts A, B and D data, we identified 1.2 million Medicare beneficiaries. We also defined a set of covariates: use of PPIs, use of H2 blockers as a control drug, admission to intensive care units or inpatient hospitals, socio-demographics, presence of 58 chronic conditions and treated them as time-dependent covariates in our main analysis of Cox proportion hazard regression. In addition to treating covariates in time-varying manner, we used the concept of lag-time to define drug exposure period in order to control for protopathic bias which occurs when the outcome of interest is associated with an exposure that actually results from early signs and symptoms of the outcome under study. This study is going to be an example of obtaining an accurate estimate of the association between drug exposure and health status. C. Fluoroquinolones and tendon complication Fluoroquinolones (FQ) are among the most widely prescribed antibiotics in the outpatient setting. Several studies have reported the plausible associations between the use of FQs and tendon complications. The U.S FDA issued black box warning labels to FQs since 2008. Several observational studies associate the use of FQ with an increased risk for tendon rupture, aortic aneurysm or dissections (AA/AD). The fact that collagen type I and III fibers provide tensile strength to both tendons and aortic walls, and that FQs can disrupt these fibers in some circumstances, magnify concerns about these reported associations. Some prior studies described the relationship between FQs and tendon rupture as a class effect and included amoxicillin as a control drug to determine whether these complications are specific to FQs. We separately included 3 FQs (ciprofloxacin, levofloxacin, moxifloxacin) and 4 non-FQ antibiotics (amoxicillin, amoxicillin-clavulanate, azithromycin or cephalexin), 5 of which were top 5 antibiotic agents in US. Using Fine-Gray competing risk regression analyses treating death as a competing risk, we assessed the independent risk of tendon rupture for each antibiotic use in a 1.2 million Medicare population. Precisely, we assessed the risk by temporal exposure within study antibiotics (within 30 days, 31-60 days, more than 60 days) to avoided non-differential misclassification that can occur with too simple (yes/no) drug exposure. The manuscript will be submitted soon. D. Association between Hormone replacement therapy and Longevity, Alzheimers disease or related dementia, cardiovascular diseases, and cancers Hormone replacement therapy (HRT) is an effective treatment for the typical menopause-related symptoms (such as hot flashes, night sweats, irregular periods and etc.) and long-term health problems associated with the menopause (the risk of osteoporosis, cardiovascular disease and stroke). Its effects on various outcomes such as Alzheimers diseases or related dementia, cardiovascular diseases, cancers and all-cause mortality is unclear. Initiation of HRT in women over 60 is generally not recommended but is found to be ok for some women after age 65. In this study, we traced about 700,000 female Medicare beneficiaries from Medicare Part D entry to the onset of each outcome, death, switching to capitated plan, disenrollment from Medicare, or 12/31/2016 whichever comes first and then we compared each risk among women treated with HRT to those not treated. Individuals in the study were grouped based on the number of days exposed to HRT (none, less than a year, more than a year) and it was treated as a time-dependent covariates in a Cox proportional hazard regression analysis. This study will explore whether or not HRT in women over 65, which is generally not recommended, reduce the risk of outcomes of interest. E. Characterizing the cardiac risks of commonly-prescribed QT-prolonging drugs Drug-induced long QT syndrome is one of the most frequent cause of withdrawal or relabeling of marketed drugs. It is difficult to detect serious adverse events associated with QT prolongation during drug development, both in the preclinical and clinical phases of drug trials. The clinical risks of many QT-prolonging drugs are only discovered by post-marketing surveillance. This study leverages the large CMS database (over 1.2 million subjects) to provide insight into the cardiac risks of some QT-prolonging drugs with known risk of severe cardiac arrhythmia (Torsades de pointes). The drugs investigated include macrolides, fluoroquinolones and antidepressants. The adverse events studied include ventricular arrhythmias, cardiac arrest and sudden death. F. Safe pregnancy and delivery Due to the low incidence of maternal death and medical complications in the pregnant population, it has always been difficult to obtain enough data for meaningful analysis in these unbalanced datasets. The National Institute of Child Health and Human Development (NICHD) collected electronic obstetric, labor and newborn data of more than 200,000 deliveries from 12 hospitals located in all nine districts of the American College of Obstetricians and Gynecologists in the U.S. Dataset includes maternal demographics, reproductive history, medical history, prenatal history of current pregnancy, labor admission assessment, labor progression, labor and delivery summary, maternal postpartum condition, newborn information and more. With the use of statistical analysis and datamining and deep learning techniques, this study leverage these information in the Consortium for Safe Labor database to uncover explore associations between antepartum and postpartum maternal co-morbidities and pregnancy outcome.